Juvenile retinoschisis with S73P, Y89C, R209C and no mutation in the XLRS1 gene

Abstract

Abstract: : Purpose: To describe the clinical phenotypes of four unrelated Japanese male patients with juvenile retinoschisis and to investigate occurrences of mutations in the XLRS1 gene. Methods: Fundus examinations, fluorescein angiography, single–flash electroretinography (ERG) were carried out. In one patient, optical coherence tomography (OCT) using an OCT3 STRATUS^TM device was performed. The coding regions of the XLRS1 gene encoding retinoschisin were amplified by polymerase chain reaction (PCR). The PCR products were purified and sequenced. Results: The four affected patients showed cystoid– or wheel–like foveal changes with little or no fluorescein leakage and negative b–wave ERG patterns in both eyes. The OCT images of foveal retinoschisis disclosed that splitting occurs in putative the fibers of Henle. In three patients, we identified three different missense mutations (p.S73P, p.Y89C, p.R209C) in the discoidin domain which is functionally important. The p.S73P mutation has not been previously reported. In contrast, any nucleotide substitutions were detected in one patient whose parents without consanguineous marriage were asymptomatic, and any other patients were not found in three generations of his pedigree. Conclusions: The Ser73 is conserved in the mouse ortholog and other discoidin proteins, the p.S73P mutation, therefore, must cause a defective function of retinoschisin. Although the inheritance pattern is uncertain in the patient without XLRS mutation, it is obvious that the clinical findings of the patient were indistinguishable from those of patients with XLRS1 mutations. This finding implicates genetic/locus heterogeneity of juvenile retinoschisis. CR: None Support: Grant #14770979, the Ministry of Education, Science and Culture of Japan (TH)

Keywords: candidate gene analysis • retinal degenerations: hereditary • genetics